Author Archives: Joshua Luchon

Who’s Going to Pay for Gene Therapy?

While gene therapy has the potential to save countless people from genetic disorders, only a select few will be able to take advantage of the technology without a price reduction. The cheapest gene therapy treatment on the market today is Yescarta, which ranges from two to four hundred thousand dollars. On the high end, Glybera comes in a whopping $1 million for a single treatment. In terms of eligible patients, Yescarta has approximately 7,500 whereas Glybera has fewer than 10. In an article published by MIT Technology Review, they examined the relationship between the cost of the treatment and the number of eligible patients. In summary, the fewer number of potential patients, the higher the cost of the treatment. This math makes sense because if the R&D is roughly equal for two drugs, but one drug can only be sold to half as many people, the pharmaceutical company needs to get more revenue from each patient. The unfortunate truth is that economics makes no concessions for patients in need of treatment.

Gene therapy treatments are expensive for several reasons, one of which is the age of the technology. In any market, the first products are always the most expensive. When the newest iPhone comes out, they never lower the price. In the pharmaceutical industry especially, the first products to market are often the most expensive to produce. While a new iPhone might have a new screen or a better camera, new medicine is the product of countless hours of research and development, which can be quite costly. FDA regulations also add to the time and cost associated with developing a new medicine or treatment, this is for good reason, but expensive nonetheless.

Sure, the first to market can command high prices, but one of the largest factors affecting the price of new medicines and treatments is the deregulation of the pharmaceutical industry. Pharmaceutical companies are given a lot of liberty in terms of pricing new drugs and they tend to charge immense premiums. In most markets, the supply is somewhat proportionate to the demand, however in specific medical treatments, the target markets are very small, meaning small demand. Companies often depend on wide customer bases to distribute the cost of development. However, the market for Glybera, the most expensive gene therapy treatment to date, consists only of patients with lipoprotein lipase deficiency, limiting the target market to less than 10 people. Since the entire cost of developing Glybera is borne by only 10 people, the price tag is astronomical. In fact, it is probably safe to assume that the developer of Glybera still lost money charging $1 million per treatment.

One of the most outspoken defenders of deregulated pricing in the pharmaceutical industry is Martin Shkreli. Infamous for buying a one of one Wu-Tang album and his smug face, Shkreli perfectly exemplifies the dangers of deregulation. In most industries, absurdly high prices simply means that customers will find cheaper alternatives, but in the pharmaceutical industry, options are limited, giving all of the power to the select few companies that produce a certain drug. Martin Shkreli took advantage of this power when he raised the price of Daraprim, a life-saving immune-system drug used to treat parasitic infection as well as AIDS and Cancer patients, by 5,000%. He raised the price of the drug from $13.50 $750 for a single pill, leaving those who depended on the drug and many others outraged. His defense for the price increase was to fund future drugs that will better help the patients. He explained that the pharmaceutical company was not profitable at $13.50 a pill and that in order to grow the company, they had to become profitable to fund research and development. His defense makes sense from a business perspective, but there are many more factors to consider when determining the cost of a life saving medicine. If pharmaceutical companies are still loosing money charging $750 a pill and $1 million per treatment while countless people can’t afford the treatments they need, how can gene therapy and the pharmaceutical industry move forward and who will pay for it?


Dr. Mark McClellan, former FDA commissioner and current leader of the Duke-Margolis Center for Health Policy, organized a consortium at Duke to analyze gene therapy treatments and to brainstorm ways to help patients pay for treatments. Through their research, the consortium concluded that the healthcare system is far behind the medical industry and the advances it has made. Generally speaking, there are three parties involved in gene therapy, the patients seeking treatment, the companies developing and pricing the treatments, and insurance companies. It is in the patient’s best interest to pay as little as possible for medicine, it is in the company’s best interest to charge the patient enough to be profitable and to pay off the development of the drug, and it is the insurance company’s job to make sure they don’t pay for any of it. Since the three major parties involved have mutually exclusive interests, it is impossible for everyone to win. Another factor to consider is the fact that patients respond differently to the treatment, meaning there is a chance that a $1 million treatment is completely ineffective. McClellan explained what is essentially a refund policy for gene therapy treatments in which patients that do not experience any relief or remission of their disease within one month are entitled to a refund. That leaves many things open to interpretation such as the definition of relief or progress, and it still does not account for the possibility of a relapse outside of the refund-window. This makes things infinitely more challenging for not only the companies administering the treatments and the patients receiving them, but it also complicates the pricing structure for insurance companies. If a patient needs coverage for a $1 million dollar one-time treatment, they have to pay out an enormous sum all at once, the one thing that keeps insurance agents up at night.

With all of the factors working against the success of gene therapy, it is hard to predict what a successful implementation will look like on a grand scale. There are countless industries that are light-years ahead of their respective regulating entities. In medicine, that disconnect prevents patients from receiving what could be a life-altering, even life-saving procedures.

Despite the current odds, Nick Leschly, CEO of Bluebird Bio, re-assures us that he’s “confident we can figure it out because if someone has a very serious disease, and we can cure it, the system will find a way to reward that.”


The Pending Implications of Gene Therapy on Education

Despite the staggering number of applications for gene therapy that are currently being investigated, the list continues to grow almost by the day. MIT researchers have discovered a potential genetic link between ADHD and Autism, meaning that gene therapy may be helpful in curing if not improving care for both disorders. The research shows that there is potentially a relationship between the brain’s thalamic reticular nucleus (TRN), which blocks out sensory inputs that can be distracting, and both ADHD and Autism. Their research suggests that when the TRN activity is slowed, the brain has a harder time controlling distractions. This means that an adjustment to the TRN behavior could help control ADHD and Autism symptoms, as well as other attention-related disorders. The study is still in its infancy and the testing is being conducted on mice, but the results are very promising. The results suggest that a correction of one specific gene, Ptchd1, carried on the X Chromosome, can restore TRN functionality.

While the research is still in the early stages, the long-term implications of a successful TRN-correction procedure are huge. The CDC estimates that 11% of children ages 4-17, accounting for 6 million children, suffer from ADHD. That is 6 million students struggling to pay attention in classrooms, struggling to focus during exams, and ultimately struggling to find employment if the symptoms persist into adulthood. If a gene editing treatment is developed, there is a possibility that those children will be able to participate and even excel in the classroom in ways they could not have fathomed without the use of prescription medicine. By eliminating the need for drugs like Adderall and Ritalin, thus eliminating children’s dependency on them, the general health of those suffering from attention disorders will improve greatly. The unfortunate reality is that disorders like ADHD condition children to depend on medicine to function properly. It is not their fault because the medicine is necessary to focus and learn, that said, it is not healthy to develop a drug dependency at such a young age regardless of its purpose.

Gene therapy is already being applied to so many genetic disorders, with the possibility of curing ADHD and Autism, a new generation of smarter, faster, healthier, and stronger people seems inevitable. There will potentially be 6 million more students studying harder, retaining more information, and ultimately becoming better learners. If this trend is multiplied across generations, eliminating prohibitive, cognitive disorders in students, it could reshape the entire education system with many subsequent disruptions. There would potentially be less of a demand for remedial education and an increase in demand for higher education or a productive alternative. This will lead to a smarter overall population, a scenario that has countless positive implications. Once of which is increased economic stimulation, resulting from the inevitable increase in demand for employment. It may be a stretch, but it is possible that one genetic modification in 6 million students could transform the entire economy.

It is easy to become caught up in the seemingly infinite number of applications for gene therapy, but the price tag is certainly a reality check. The current price for Yescarta, a patient-specific gene therapy procedure designed to treat aggressive forms of blood cancer, is a whopping $373,000. At that price point, it makes far more sense to treat attention disorders such as ADHD with prescription drugs. However, as the technology evolves, the price will inevitably come down. We are in a strange transition period in many different industries and medicine is no exception. The new advancements being made are nothing short of groundbreaking, but it is no small task to bring a new procedure to the market. Due to FDA regulations, years of research and testing are required before the first human trials, and even then, successful implementation into the market is not guaranteed. In medicine, consumer demand for treatments is ahead of the technology, and the technology is way ahead of the FDA. This may slow down the implementation of new drugs and procedures, but their timelines do not detract in any way from the scope and severity of their implications.



Gene Therapy Update: How it Works and Why it’s Risky

Gene therapy has the potential to be the most innovative and disruptive medical procedure in the modern world, but it is still in its earliest stages of development. Technology moves faster than any other industry on the planet, but when paired with science and medicine, the pace may be so fast that it becomes detrimental. Gene therapy is equal parts technology and medicine and there will be an eternal struggle between the two. From a technological standpoint, it’s full steam ahead for companies like CRISPR. For those focused on the medical side however, there is a long road ahead. It is important to remember that the success of gene therapy depends first on the development of the technology, but without testing and a safe implementation in the medical field, no lives will be saved. It is much different than Silicon Valley pushing Face ID or a new app because in both of those instances, the faster the technology is available to consumers the better, or so they have us believe. When Apple pushes new tech like Face ID, they know that they can usually work out the bugs with a software update, but things aren’t that simple when the technology involves pumping new genes into people’s bodies.

The science behind gene therapy is just as amazing as the technology behind deciding which specific genes need attention. In order for a patient to receive the treatment, the new genes must be introduced into the body via a number of possible procedures. The most common of which include specifically placed injections or IV treatments, depending on the disease the treatment is aimed to fight and where the problem is within the body. Once inside the body however, the procedure is essentially the same. The new or modified genes are brought to their desired locations using a vector. The most common vectors are bacteria, viruses, and plasmids. They are the most common because while they are completely different, they all share the essential characteristic of being able to multiply quickly once in a cell. Under normal circumstances, their hyperactivity is a bad thing because it is the very reason that diseases are able to spread so quickly. In gene therapy however, this trait makes them the perfect candidates to transport genes. The video below provides a visual demonstration of this process during a treatment of a retinal disease.

The use of vectors is relatively consistent across all forms of gene therapy, however, there are several different methods used to treat different diseases. On the most basic level, there are two forms of gene therapy, somatic and germline. Somatic treatments are targeted at cells that do not produce eggs or sperm, therefore the treatment will not be passed down to subsequent generations. Conversely, germline treatments target cells that do produce sperm or eggs, which means that any alterations made to cells in the patient’s body will be passed down. Germline treatments are arguably more dangerous because if something goes wrong during the procedure or if the new genes are incorrect, the faulty DNA will be passed down until it is corrected by another procedure.

Under the umbrella of somatic and germline treatments are three main forms of therapies that vary depending on the problem. The therapies include gene augmentation, gene inhibition, and targeted cell attacks. Gene augmentation is used when a cell has faulty DNA that needs to be corrected. In this case, the new genes are attached to a vector that will reproduce in the desired cells, and will replace the existing DNA in the hopes of delivering the correct directions. Gene inhibition does the opposite, as gene inhibition treatments are designed to stop cells from behaving a certain way instead of correcting an undesired behavior. This form of gene therapy is useful for treating cancer patients because the goal is to slow down the reproduction of cancerous cells. This is achieved by attaching genes to a vector that will tell the cancerous cells to stop reproducing. Doctors also have the ability to target a cluster of cells that they wish to eliminate altogether. This is achieved by either injecting vectors that will kills the cells directly, or by using vectors that will trigger an immune system response which will in turn kill the desired cells. This is slightly less effective because the vectors are used to trick the body into fighting a disease that it did not otherwise recognize. Regardless of the objective of the various forms of gene therapy, vectors are the most effective vehicles to deliver new genes to cells.

While the vectors are very useful for delivering the new genes to their desired targets, there are many risks involved with the procedure. Success of the treatment aside, there are risks associated with the injection alone. It is a high-risk procedure because while it can be extremely effective, it can just as easily catalyze a series of detrimental reactions within the body. If the new DNA is delivered to the wrong cells, it can disrupt necessary functionality completely unrelated to the disease it was aimed to fight. If the vectors used in the procedure trigger an unexpected immune system response, the treatment can be rejected altogether or in some cases even cause organs to fail.

Jesse Gelsinger’s story serves as a grim reminder of the unintended consequences of gene therapy. Jesse suffered from a rare metabolic disorder called ornithine transcarbamylase (OTC) deficiency, which made him an ideal candidate for a gene therapy experiment at the University of Pennsylvania. The vector that was used in the procedure was a weakened cold virus which was delivered via injections. The doctors at Penn had tested their vector on mice, baboons, monkeys, and one other human patient, so they were confident that Jesse had a real chance of improving. What the doctors did not predict, was the overwhelming inflammatory response that started a chain reaction in Jesse’s body. A mere 24 hours after the injection, there was 11 times the normal amount of ammonia in Jesse’s blood, he was hyperventilating, his ears had swollen shut, he had developed a blood clotting disorder called jaundice, his kidneys were starting to fail along with his lungs, and his brain had started to shut down. Shortly after the doctors thought they had things under control, Jesse died. His death marked the first documented casualty resulting from gene therapy and left the doctors in shock.

Jesse’s premature death exemplifies the uncertainty involved with gene therapy, and there will undoubtedly be others. The technology is so new that is impossible to predict the outcome of the treatments with any degree of certainty. On paper, Jesse’s treatment should have worked but all of the years of testing and analysis that took place before the procedure were flipped upside down when his body started to reject the treatment. The best doctors in the world cannot explain what caused Jesse’s body to react the way it did which speaks to the unpredictable nature of the technology. Gene therapy is an amazing advancement for both technology and medicine, but it is still wildly imperfect and will require many more brave patients like Jesse before it becomes a dependable procedure.